Issue
Korean Journal of Chemical Engineering,
Vol.25, No.1, 108-111, 2008
Purification of homoharringtonine and removal of residual solvents by spray drying
Homoharringtonine was purified from Cephalotaxus koreana by a combination of extraction, synthetic adsorbent treatment, low-pressure chromatography, and high performance liquid chromatography (HPLC). A crude extract was obtained by methanol extraction of biomass, followed by liquid-liquid extraction using chloroform. The waxy compounds were efficiently removed by adsorbent (active clay P-1) treatment. The extract was purified to greater than 52% with an 86.4% step yield by silica gel low-pressure chromatography. High performance liquid chromatography steps, which were composed of an HPLC step with silica column and an HPLC step with ODS column, were applied to give 98% purity with high yield. Amorphous homoharringtonine, with a fine particle size, was simply made by dissolving homoharringtonine in methylene chloride/methanol (98/2, v/v), followed by spray drying. Residual solvents, methylene chloride and methanol, could be reduced to 250 ppm and 1,160 ppm by spray drying and successive drying in a vacuum oven.
[References]
  1. Grem JL, Cheson BD, King SA, Leyland-Jones B, Suffness M, J. Natl. Cancer Inst., 80, 1095, 1988
  2. He J, Cheung AP, Wang E, Struble E, Fang K, Nguyen N, Liu P, J. Pharm. Biomed. Anal., 22, 541, 2000
  3. Zhou DC, Zittoun R, Marie JP, Bull. Cancer., 82, 987, 1995
  4. Luo CY, Tang JY, Wang YP, Hematology, 9, 259, 2004
  5. Xie WZ, Lin MF, Huang H, Cai Z, Am. J. Chin. Med., 34, 233, 2006
  6. Jin J, Jiang DZ, Mai WY, Meng HT, Qian WB, Tong HY, Huang J, Mao LP, Tong Y, Wang L, Chen ZM, Xu WL, Leukemia, 3, 1361, 2006
  7. Beverly AB, Myron NC, Howard JW, Med. Pediatr. Oncol., 37, 103, 2000
  8. Kantarjian HM, Talpaz M, Santini V, Murgo A, Cheson B, O’Brien SM, Cancer, 15, 1591, 2001
  9. Efferth T, Davey M, Olbrich A, Rucker G, Gebhart E, Davey R, Blood Cells Mol. Dis., 28, 160, 2002
  10. Wang DZ, Ma GE, Xu RS, Yaoxue Xuebao, 27, 178, 1992
  11. Keller L, Dumas F, d’Angelo J, Tetrahedron Lett., 42, 1911, 2001
  12. Liu Y, US Patent, 4,783,454, 1988
  13. Castor TP, US Patent, 5,750,709, 1998
  14. Kim JH, Kang IS, Choi HK, Hong SS, Lee HS, Biotechnol. Lett., 22(22), 1753, 2000
  15. Gi US, Min B, Lee JH, Kim JH, Korean J. Chem. Eng., 21(4), 816, 2004
  16. ICH guidance Q3C impurities: Residual solvents, Federal register, 62(247), 67378, 1997